Trial Outcomes & Findings for A Drug Interaction Study to Assess the Pharmacokinetics of Narlaprevir and Antiretroviral Drugs (NCT NCT03537404)

NCT ID: NCT03537404

Last Updated: 2019-02-19

Results Overview

Maximum observed Concentration of Narlaprevir at Day 5 of treatment A and C of Part 1 or 2 of the study

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 36 participants
• Primary outcome timeframe: Day 5 Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours post-dose on Day 5 of treatment A and C (Part 1/ Part 2)
• Results posted on: 2019-02-19

Participant Flow

Healthy adult volunteers were recruited for all Parts of the study in one clinical site (Bessalar clinic) in Moscow between April and June 2017. 36 subjects were randomized so that 18 subjects participated in each Part of the study (6 subjects in each treatment group of each Part).

Subjects were to be screened within 28 days before dosing in this multi-part study. Subjects were to be admitted to the study center the evening before the first dose for baseline assessments to confirm eligibility.

Participant milestones

Measure	Part 1 All patients of Part 1 of the study were randomized in 1:1:1 ratio to receive one of the treatment sequences (A/B/C, B/C/A or C/A/B). Every subject received only one drug combination (A or B or C) in one treatment period. Each period was followed by 8 washout days. Treatments include: Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily); Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily); Tenofovir Disoproxil Fumarate (300 mg, film-coated tablets, taken as 300 mg per os once daily) in different combinations assigned to the subjects in accordance with protocol considerations for Part 1 of the study.	Part 2 All patients of Part 2 of the study were randomized in 1:1:1 ratio to receive one of the treatment sequences (A/B/C, B/C/A or C/A/B). Every subject received only one drug combination (A or B or C) in one treatment period. Each period was followed by 8 washout days. Treatments include: Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily); Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily); Raltegravir (400 mg, film-coated tablets, taken as 400 mg per os once daily) in different combinations assigned to the subjects in accordance with protocol considerations for Part 2 of the study.
First Intervention (A or B or C) STARTED	18	18
First Intervention (A or B or C) COMPLETED	18	18
First Intervention (A or B or C) NOT COMPLETED	0	0
First Washout Period (8 Days) STARTED	18	18
First Washout Period (8 Days) COMPLETED	18	18
First Washout Period (8 Days) NOT COMPLETED	0	0
Second Intervention (A or B or C) STARTED	18	18
Second Intervention (A or B or C) COMPLETED	18	18
Second Intervention (A or B or C) NOT COMPLETED	0	0
Second Washout Period (8 Days) STARTED	18	18
Second Washout Period (8 Days) COMPLETED	18	18
Second Washout Period (8 Days) NOT COMPLETED	0	0
Third Intervention (A or B or C) STARTED	18	18
Third Intervention (A or B or C) COMPLETED	18	18
Third Intervention (A or B or C) NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).

Baseline characteristics by cohort

Measure	Sequence A/B/C n=12 Participants All participants of Part 1 or 2 of the study randomized in this group received treatment combinations (according to the protocol allocation) in the following sequence: Treatment period 1 - Treatment A Treatment period 2 - Treatment B Treatment period 3 - Treatment C	Sequence B/C/A n=12 Participants All participants of Part 1 or 2 of the study randomized in this group received treatment combinations (according to the protocol allocation) in the following sequence: Treatment period 1 - Treatment B Treatment period 2 - Treatment C Treatment period 3 - Treatment A	Sequence C/A/B n=12 Participants All participants of Part 1 or 2 of the study randomized in this group received treatment combinations (according to the protocol allocation) in the following sequence: Treatment period 1 - Treatment C Treatment period 2 - Treatment A Treatment period 3 - Treatment B	Total n=36 Participants Total of all reporting groups
Age, Continuous Part 1	24.3 years STANDARD_DEVIATION 1.75 • n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	38.3 years STANDARD_DEVIATION 8.26 • n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	29.7 years STANDARD_DEVIATION 1.86 • n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	30.8 years STANDARD_DEVIATION 7.57 • n=18 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).
Age, Continuous Part 2	24.3 years STANDARD_DEVIATION 4.03 • n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	38.7 years STANDARD_DEVIATION 4.59 • n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	29.5 years STANDARD_DEVIATION 3.33 • n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	30.8 years STANDARD_DEVIATION 7.17 • n=18 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).
Sex: Female, Male Part 1 · Female	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	0 Participants n=18 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).
Sex: Female, Male Part 1 · Male	6 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	6 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	6 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	18 Participants n=18 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).
Sex: Female, Male Part 2 · Female	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	0 Participants n=18 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).
Sex: Female, Male Part 2 · Male	6 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	6 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	6 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	18 Participants n=18 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).
Race/Ethnicity, Customized Part 1 · White	6 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	6 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	5 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	17 Participants n=18 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).
Race/Ethnicity, Customized Part 1 · Asian	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	1 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	1 Participants n=18 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).
Race/Ethnicity, Customized Part 1 · Black	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	0 Participants n=18 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).
Race/Ethnicity, Customized Part 1 · Other	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	0 Participants n=18 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).
Race/Ethnicity, Customized Part 2 · White	6 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	5 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	6 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	17 Participants n=18 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).
Race/Ethnicity, Customized Part 2 · Asian	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	1 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	1 Participants n=18 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).
Race/Ethnicity, Customized Part 2 · Black	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	0 Participants n=18 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).
Race/Ethnicity, Customized Part 2 · Other	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	0 Participants n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	0 Participants n=18 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).
Body Mass Index (BMI) Part 1	23.14 kg/m2 STANDARD_DEVIATION 1.287 • n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	24.73 kg/m2 STANDARD_DEVIATION 3.022 • n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	24.20 kg/m2 STANDARD_DEVIATION 3.134 • n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	24.02 kg/m2 STANDARD_DEVIATION 2.554 • n=18 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).
Body Mass Index (BMI) Part 2	24.26 kg/m2 STANDARD_DEVIATION 4.132 • n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	25.40 kg/m2 STANDARD_DEVIATION 2.732 • n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	25.63 kg/m2 STANDARD_DEVIATION 3.408 • n=6 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).	25.10 kg/m2 STANDARD_DEVIATION 3.319 • n=18 Participants • Baseline characteristics analisys was performed separately for Part 1 and 2 of the study (18 subjects in each Part were randomized in 1:1:1 ratio for each treatment sequence - 6 participants in each).

PRIMARY outcome

Timeframe: Day 5 Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours post-dose on Day 5 of treatment A and C (Part 1/ Part 2)

Population: All subjects randomized to study treatment and received at least one dose of study drug.

Maximum observed Concentration of Narlaprevir at Day 5 of treatment A and C of Part 1 or 2 of the study

Outcome measures

Measure	Treatment A (Part 1) n=18 Participants Subjects in both Parts of the study recieved as Treatment A for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) and Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily).	Treatment C (Part 1) n=18 Participants Subjects recieved as Treatment C for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) coadministered with Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily) and Tenofovir Disoproxil Fumarate (300 mg, film-coated tablets, taken as 300 mg per os once daily).	Treatment A (Part 2) n=18 Participants Subjects in both Parts of the study recieved as Treatment A for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) and Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily).	Treatment C (Part 2) n=18 Participants Subjects recieved as Treatment C for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) coadministered with Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily and Raltegravir (400 mg, film-coated tablets, taken as 400 mg per os twice daily).	Treatment B (Part 2) Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days	Treatment C (Part 2) Narlaprevir, 100 mg, film-coated tablets, taken as 200 mg per os daily coadministered with Ritonavir, 100 mg, film-coated tablets, taken as 100 mg per os daily and Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days
Cmax of Narlaprevir	2130.2742 ng/ml Interval 1817.4088 to 2731.8348	2172.233 ng/ml Interval 1895.673 to 2726.557	2946.131 ng/ml Interval 2617.485 to 3799.642	2880.612 ng/ml Interval 2412.858 to 4121.871	—	—

PRIMARY outcome

Timeframe: Day 5 Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours post-dose on Day 5 of treatment A and C (Part 1/ Part 2)

Population: All subjects randomized to study treatment and received at least one dose of study drug.

Area Under the Concentration-time curve during a dosing interval τ at steady state of Narlaprevir at Day 5 of treatment A and C of Part 1/ Part 2 of the study

Outcome measures

Measure	Treatment A (Part 1) n=18 Participants Subjects in both Parts of the study recieved as Treatment A for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) and Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily).	Treatment C (Part 1) n=18 Participants Subjects recieved as Treatment C for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) coadministered with Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily) and Tenofovir Disoproxil Fumarate (300 mg, film-coated tablets, taken as 300 mg per os once daily).	Treatment A (Part 2) n=18 Participants Subjects in both Parts of the study recieved as Treatment A for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) and Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily).	Treatment C (Part 2) n=18 Participants Subjects recieved as Treatment C for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) coadministered with Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily and Raltegravir (400 mg, film-coated tablets, taken as 400 mg per os twice daily).	Treatment B (Part 2) Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days	Treatment C (Part 2) Narlaprevir, 100 mg, film-coated tablets, taken as 200 mg per os daily coadministered with Ritonavir, 100 mg, film-coated tablets, taken as 100 mg per os daily and Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days
AUCtau of Narlaprevir	20504.31 ng*h/ml Interval 18265.63 to 24328.95	21366.2 ng*h/ml Interval 18664.1 to 26481.9	26199.19 ng*h/ml Interval 23136.15 to 33132.53	24458.48 ng*h/ml Interval 20738.76 to 33597.42	—	—

PRIMARY outcome

Timeframe: Day 5 Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 18 and 24 hrs post-dose on Day 5 of treatment B and C (Part 1)

Population: All subjects randomized to study treatment and received at least one dose of study drug.

Maximum observed Concentration of Tenofovir at Day 5 of treatment B and C of Part 1 of the study

Outcome measures

Measure	Treatment A (Part 1) n=18 Participants Subjects in both Parts of the study recieved as Treatment A for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) and Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily).	Treatment C (Part 1) n=18 Participants Subjects recieved as Treatment C for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) coadministered with Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily) and Tenofovir Disoproxil Fumarate (300 mg, film-coated tablets, taken as 300 mg per os once daily).	Treatment A (Part 2) Subjects in both Parts of the study recieved as Treatment A for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) and Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily).	Treatment C (Part 2) Subjects recieved as Treatment C for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) coadministered with Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily and Raltegravir (400 mg, film-coated tablets, taken as 400 mg per os twice daily).	Treatment B (Part 2) Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days	Treatment C (Part 2) Narlaprevir, 100 mg, film-coated tablets, taken as 200 mg per os daily coadministered with Ritonavir, 100 mg, film-coated tablets, taken as 100 mg per os daily and Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days
Cmax of Tenofovir	263.037 ng/ml Interval 233.126 to 313.318	344.796 ng/ml Interval 302.457 to 415.092	—	—	—	—

PRIMARY outcome

Timeframe: Day 5 Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 18 and 24 hrs post-dose on Day 5 of treatment B and C (Part 1)

Population: All subjects randomized to study treatment and received at least one dose of study drug.

Area Under the Concentration-time curve during a dosing interval τ at steady state of Tenofovir at Day 5 of treatment B and C of Part 1 of the study

Outcome measures

Measure	Treatment A (Part 1) n=18 Participants Subjects in both Parts of the study recieved as Treatment A for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) and Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily).	Treatment C (Part 1) n=18 Participants Subjects recieved as Treatment C for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) coadministered with Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily) and Tenofovir Disoproxil Fumarate (300 mg, film-coated tablets, taken as 300 mg per os once daily).	Treatment A (Part 2) Subjects in both Parts of the study recieved as Treatment A for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) and Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily).	Treatment C (Part 2) Subjects recieved as Treatment C for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) coadministered with Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily and Raltegravir (400 mg, film-coated tablets, taken as 400 mg per os twice daily).	Treatment B (Part 2) Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days	Treatment C (Part 2) Narlaprevir, 100 mg, film-coated tablets, taken as 200 mg per os daily coadministered with Ritonavir, 100 mg, film-coated tablets, taken as 100 mg per os daily and Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days
AUCtau of Tenofovir	2599.95 ng*h/ml Interval 2325.72 to 3043.02	2799.72 ng*h/ml Interval 2536.67 to 3205.65	—	—	—	—

PRIMARY outcome

Timeframe: Day 5 Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12 hrs post-dose of Day 5 of treatment B and C (Part 2)

Population: All subjects randomized to study treatment and received at least one dose of study drug.

Maximum observed Concentration of Raltegravir at Day 5 of treatment B and C of Part 2 of the study

Outcome measures

Measure	Treatment A (Part 1) n=18 Participants Subjects in both Parts of the study recieved as Treatment A for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) and Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily).	Treatment C (Part 1) n=18 Participants Subjects recieved as Treatment C for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) coadministered with Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily) and Tenofovir Disoproxil Fumarate (300 mg, film-coated tablets, taken as 300 mg per os once daily).	Treatment A (Part 2) Subjects in both Parts of the study recieved as Treatment A for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) and Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily).	Treatment C (Part 2) Subjects recieved as Treatment C for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) coadministered with Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily and Raltegravir (400 mg, film-coated tablets, taken as 400 mg per os twice daily).	Treatment B (Part 2) Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days	Treatment C (Part 2) Narlaprevir, 100 mg, film-coated tablets, taken as 200 mg per os daily coadministered with Ritonavir, 100 mg, film-coated tablets, taken as 100 mg per os daily and Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days
Cmax of Raltegravir	830.204 ng/ml Interval 520.042 to 2758.109	715.726 ng/ml Interval 136.163 to 2396.13	—	—	—	—

PRIMARY outcome

Timeframe: Day 5 Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12 hrs post-dose of Day 5 of treatment B and C (Part 2)

Population: All subjects randomized to study treatment and received at least one dose of study drug.

Area Under the Concentration-time curve during a dosing interval τ at steady state of Tenofovir at Day 5 of treatment B and C of Part 2 of the study

Outcome measures

Measure	Treatment A (Part 1) n=18 Participants Subjects in both Parts of the study recieved as Treatment A for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) and Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily).	Treatment C (Part 1) n=18 Participants Subjects recieved as Treatment C for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) coadministered with Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily) and Tenofovir Disoproxil Fumarate (300 mg, film-coated tablets, taken as 300 mg per os once daily).	Treatment A (Part 2) Subjects in both Parts of the study recieved as Treatment A for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) and Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily).	Treatment C (Part 2) Subjects recieved as Treatment C for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) coadministered with Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily and Raltegravir (400 mg, film-coated tablets, taken as 400 mg per os twice daily).	Treatment B (Part 2) Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days	Treatment C (Part 2) Narlaprevir, 100 mg, film-coated tablets, taken as 200 mg per os daily coadministered with Ritonavir, 100 mg, film-coated tablets, taken as 100 mg per os daily and Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days
AUCtau of Raltegravir	2912.45 ng*h/ml Interval 1983.01 to 8451.44	2653.65 ng*h/ml Interval 1033.88 to 6964.58	—	—	—	—

SECONDARY outcome

Timeframe: Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study

Population: All subjects randomized to study treatment and received at least one dose of study drug

Outcome measures

Measure	Treatment A (Part 1) n=18 Participants Subjects in both Parts of the study recieved as Treatment A for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) and Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily).	Treatment C (Part 1) n=18 Participants Subjects recieved as Treatment C for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) coadministered with Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily) and Tenofovir Disoproxil Fumarate (300 mg, film-coated tablets, taken as 300 mg per os once daily).	Treatment A (Part 2) n=18 Participants Subjects in both Parts of the study recieved as Treatment A for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) and Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily).	Treatment C (Part 2) n=18 Participants Subjects recieved as Treatment C for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) coadministered with Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily and Raltegravir (400 mg, film-coated tablets, taken as 400 mg per os twice daily).	Treatment B (Part 2) n=18 Participants Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days	Treatment C (Part 2) n=18 Participants Narlaprevir, 100 mg, film-coated tablets, taken as 200 mg per os daily coadministered with Ritonavir, 100 mg, film-coated tablets, taken as 100 mg per os daily and Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days
Number of Patients With Adverse Events	1 Participants	0 Participants	4 Participants	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study

Population: All subjects randomized to study treatment and received at least one dose of study drug

There were no subjects with abnormal changes in vital signs

Outcome measures

Measure	Treatment A (Part 1) n=18 Participants Subjects in both Parts of the study recieved as Treatment A for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) and Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily).	Treatment C (Part 1) n=18 Participants Subjects recieved as Treatment C for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) coadministered with Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily) and Tenofovir Disoproxil Fumarate (300 mg, film-coated tablets, taken as 300 mg per os once daily).	Treatment A (Part 2) n=18 Participants Subjects in both Parts of the study recieved as Treatment A for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) and Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily).	Treatment C (Part 2) n=18 Participants Subjects recieved as Treatment C for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) coadministered with Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily and Raltegravir (400 mg, film-coated tablets, taken as 400 mg per os twice daily).	Treatment B (Part 2) n=18 Participants Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days	Treatment C (Part 2) n=18 Participants Narlaprevir, 100 mg, film-coated tablets, taken as 200 mg per os daily coadministered with Ritonavir, 100 mg, film-coated tablets, taken as 100 mg per os daily and Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days
Number of Patients With Changes in Vital Signs	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study

Population: All subjects randomized to study treatment and received at least one dose of study drug separately for each Patr of the study

Outcome measures

Measure	Treatment A (Part 1) n=18 Participants Subjects in both Parts of the study recieved as Treatment A for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) and Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily).	Treatment C (Part 1) n=18 Participants Subjects recieved as Treatment C for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) coadministered with Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily) and Tenofovir Disoproxil Fumarate (300 mg, film-coated tablets, taken as 300 mg per os once daily).	Treatment A (Part 2) n=18 Participants Subjects in both Parts of the study recieved as Treatment A for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) and Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily).	Treatment C (Part 2) Subjects recieved as Treatment C for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) coadministered with Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily and Raltegravir (400 mg, film-coated tablets, taken as 400 mg per os twice daily).	Treatment B (Part 2) Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days	Treatment C (Part 2) Narlaprevir, 100 mg, film-coated tablets, taken as 200 mg per os daily coadministered with Ritonavir, 100 mg, film-coated tablets, taken as 100 mg per os daily and Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days
Number of Patients With Abnormal Laboratory Values Part 1	0 Participants	0 Participants	2 Participants	—	—	—
Number of Patients With Abnormal Laboratory Values Part 2	0 Participants	0 Participants	1 Participants	—	—	—

SECONDARY outcome

Timeframe: Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study

Population: All subjects randomized to study treatment and received at least one dose of study drug

There were no subjects with abnormal ECG changes during the study

Outcome measures

Measure	Treatment A (Part 1) n=18 Participants Subjects in both Parts of the study recieved as Treatment A for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) and Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily).	Treatment C (Part 1) n=18 Participants Subjects recieved as Treatment C for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) coadministered with Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily) and Tenofovir Disoproxil Fumarate (300 mg, film-coated tablets, taken as 300 mg per os once daily).	Treatment A (Part 2) n=18 Participants Subjects in both Parts of the study recieved as Treatment A for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) and Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily).	Treatment C (Part 2) Subjects recieved as Treatment C for 5 days (in respective treatment period): Narlaprevir (100 mg, film-coated tablets, taken as 200 mg per os once daily) coadministered with Ritonavir (100 mg, film-coated tablets, taken as 100 mg per os once daily and Raltegravir (400 mg, film-coated tablets, taken as 400 mg per os twice daily).	Treatment B (Part 2) Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days	Treatment C (Part 2) Narlaprevir, 100 mg, film-coated tablets, taken as 200 mg per os daily coadministered with Ritonavir, 100 mg, film-coated tablets, taken as 100 mg per os daily and Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days
Number of Patients With Abnormal ECG Changes Part 1	0 Participants	0 Participants	0 Participants	—	—	—
Number of Patients With Abnormal ECG Changes Part 2	0 Participants	0 Participants	0 Participants	—	—	—

Adverse Events

Treatment A (Part 1)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Treatment B (Part 1)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Treatment C (Part 1)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Treatment A (Part 2)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Treatment B (Part 2)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Treatment C (Part 2)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Treatment A (Part 1) n=18 participants at risk Narlaprevir, 100 mg, film-coated tablets, taken as 200 mg per os daily in combination with Ritonavir, 100 mg, film-coated tablets, taken as 100 mg per os daily for 5 days	Treatment B (Part 1) n=18 participants at risk Tenofovir Disoproxil Fumarate, 300 mg, film-coated tablets, taken as 300 mg per os daily for 5 days	Treatment C (Part 1) n=18 participants at risk Narlaprevir, 100 mg, film-coated tablets, taken as 200 mg per os daily coadministered with Ritonavir, 100 mg, film-coated tablets, taken as 100 mg per os daily and Tenofovir Disoproxil Fumarate, 300 mg, film-coated tablets, taken as 300 mg per os daily for 5 days	Treatment A (Part 2) n=18 participants at risk Narlaprevir, 100 mg, film-coated tablets, taken as 200 mg per os daily in combination with Ritonavir, 100 mg, film-coated tablets, taken as 100 mg per os daily for 5 days	Treatment B (Part 2) n=18 participants at risk Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days	Treatment C (Part 2) n=18 participants at risk Narlaprevir, 100 mg, film-coated tablets, taken as 200 mg per os daily coadministered with Ritonavir, 100 mg, film-coated tablets, taken as 100 mg per os daily and Raltegravir, 400 mg, film-coated tablets, taken as 400 mg per os daily for 5 days
Investigations Alanine Aminotransferase Increased	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	5.6% 1/18 • Number of events 1 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	5.6% 1/18 • Number of events 1 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study
Investigations Blood Lactate Dehydrogenase Decreased	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	5.6% 1/18 • Number of events 1 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study
Nervous system disorders Headache	5.6% 1/18 • Number of events 1 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	5.6% 1/18 • Number of events 1 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study
Gastrointestinal disorders Diarrhoea	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	5.6% 1/18 • Number of events 1 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study
Investigations Gamma-Glutamyltransferase Increased	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	0.00% 0/18 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study	5.6% 1/18 • Number of events 1 • Up to 14 Days after the last dose of treatment in period 3 of each Part of the Study

Additional Information

Emiliya Krasavina, Medical Adviser

R-Pharm

Phone: 0074959567937

Email: krasavina@rpharm.ru

Results disclosure agreements

• Principal investigator is a sponsor employee Any study related information could be made public availiable only after Sponsors written permission.
• Publication restrictions are in place

Restriction type: OTHER